Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?

The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.     

Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.     

HDL3-mediated cholesterol efflux from cultured enterocytes: The role of apoproteins A-I and A-II

High density lipoproteins (HDL) were recently demonstrated in an enterocyte model (CaCo-2 cells) to mediate reverse cholesterol transport by retroendocytosis. The present study was carried out to define the role of the major HDL apoproteins (apo) A-I and apo A-II in this pathway. HDL₃ was fractionated by heparin affinity chromatography into the two main fractions containing either apo A-I only (fraction A) or both apo A-I and apo A-II (fraction B). In addition, liposomes were reconstituted from purified apo A-I or apo A-II and dimyristoyl phosphatidylcholine. The cell binding properties and cholesterol efflux potential were studied in the lipoprotein fractions and the liposomes. Both fractions exhibited similar maximal binding capacities of 4427 (A) and 5041 (B) ng/mg cell protein, but their dissociation constants differed (40.5 and 167.7 μg/mL, respectively). Fraction A induced cholesterol efflux and stimulated cholesterol synthesis more than did fraction B. Fraction A mobilized both cellular free and esterified cholesterol, whereas fraction B preferentially mobilized cholesteryl esters. Liposomes, containing either apo A-I or apo A-II, showed specific binding, endocytosis and endosomal transport, and were released as intact particles. Apo A-I liposomes also mediated cholesterol efflux. In conclusion, there is evidence that the HDL₃ subfractions A and B, as well as reconstituted liposomes containing either apo A-I or apo A-II, were specifically bound and entered a retroendocytosis pathway which was directly linked to cholesterol efflux. Quantitatively, the apo A-I subfraction appeared to play the dominant role in normal enterocytes. The apo A-II content of fraction B was related to the mobilization of cholesteryl esters.     

Insertion du chlore dans le graphite

The action of liquid chlorine on graphite has been studied by gravimetric, dilatometric and radiocrystallographic means. Around ?20°C and according to the nature of the graphite, the compounds C₁₂Cl and C₁₆Cl corresponding to stages 3 and 4 respectively, were obtained. The interplanar distance is practically double that of pure graphite or 6.70 Å. The intercalation involves a decrease in electrical resistivity in the direction parallel to the layers comparable to that observed for bromine. It was not possible to prepare compounds richer in chlorine by cooling to ?40 and ?78°C.     

Hydroisomerization of Renewable and Fossil n-Alkanes over Bifunctional Dealuminated ZSM-5 Catalysts

The hydroisomerization of two long-chain n-alkane mixtures was investigated over bifunctional Pt/H-ZSM-5 catalysts before and after dealumination of preshaped zeolite/binder pellets. The hydroisomerization over the dealuminated catalysts leads to more isomers and less cracking products. Consequently, higher ratios of multi- to mono-branched isomerization products are formed as expected for large- rather than medium-pore zeolites. This indicates a higher availability of space in the vicinity of the active sites and provides an attractive route to make medium-pore zeolites suitable for upgrading higher boiling hydrocarbon feeds.     

Some challenges in global land cover mapping: An assessment of agreement and accuracy in existing 1 km datasets

Many investigators need and use global land cover maps for a wide variety of purposes. Ironically, after many years of very limited availability, there are now multiple global land cover maps and it is not readily apparent (1) which is most useful for particular applications or (2) how to combine the different maps to provide an improved dataset. The existing global land cover maps at 1 km spatial resolution have arisen from different initiatives and are based on different remote sensing data and employed different methodologies. Perhaps more significantly, they have different legends. As a result, comparison of the different land cover maps is difficult and information about their relative utility is limited. In an attempt to compare the datasets and assess their strengths and weaknesses we harmonized the thematic legends of four available coarse-resolution global land cover maps (IGBP DISCover, UMD, MODIS 1-km, and GLC2000) using the LCCS-based land cover legend translation protocols. Analysis of the agreement among the global land cover maps and existing validation information highlights general patterns of agreement, inconsistencies and uncertainties. The thematic classes of Evergreen broadleaf trees, Snow and Ice, and Barren show high producer and user accuracy and good agreement among the datasets, while classes of mixed tree types show high commission errors. Overall, the results show a limited ability of the four global products to discriminate mixed classes characterized by a mosaic of trees, shrubs, and herbaceous vegetation. There is a strong relationship between class accuracy, spatial agreement among the datasets, and the heterogeneity of landscapes. Suggestions for future mapping projects include careful definition of mixed unit classes, and improvement in mapping heterogeneous landscapes.     

Mediating Media Studies – Stimulating critical awareness in a virtual environment

Second Life has become increasingly popular with educators and educational institutions, because of the educational possibilities it seems to offer. While there has been a lot of hype and academic publications about educational design or the theoretical framing of teaching in virtual environments, there have been few publications focussing on actual teaching and learning experiences of lecturers and students in Higher Education institutions. This article uses practical examples from an introductory course on Media studies taught at the Hong Kong Polytechnic University to demonstrate that even simple tasks in Second Life can be used to great effect if properly contextualised into the course being taught. High levels of technical skills, or extraordinary educational designs are less important to employing Second Life successfully in a Higher Education environment, than a proper evaluation of student learning outcomes, and teaching goals.     

Clotrimazole-loaded Eudragit® RS100 nanocapsules: Preparation,characterization and in vitro evaluation of antifungal activity against Candida species

Clotrimazole is a common choice for the treatment of vulvovaginal infections, but its low solubility and some side effects pose a challenge to its application. This work evaluated the feasibility to formulate clotrimazole-loaded cationic nanocapsules using Eudragit® RS100 and medium chain triglycerides as polymer and oily core, respectively, by the method of interfacial deposition of a preformed polymer. The physicochemical characteristics of nanocapsule formulations were evaluated at 0 day and 60 days after preparation. Particle size, zeta potential, polydispersity index, pH and drug content were stable during this period. In addition, nanocapsules were able to protect clotrimazole from photodegradation under UV radiation. By the dialysis bag diffusion technique, the nanosized formulations showed prolonged release of clotrimazole by anomalous transport and first order kinetics. A microbiological study was carried out by the microdilution method and showed that nanocapsules (mean size: 144 nm; zeta potential: + 12 mV) maintained the antifungal activity of clotrimazole against Candida albicans and Candida glabrata strains susceptible and resistant to fluconazole.     

Extending the technology acceptance model to explore the intention to use Second Life for enhancing healthcare education

Learners need to have good reasons to engage and accept e-learning. They need to understand that unless they do, the outcomes will be less favourable. The technology acceptance model (TAM) is the most widely recognized model addressing why users accept or reject technology. This study describes the development and evaluation of a virtual environment, the online 3D world Second Life (SL), for learning rapid sequence intubation (RSI). RSI is an increasingly frequently used method of acute airway management in healthcare settings. The intention of learners to use the system was explored based on the TAM, with the computer self-efficacy construct as an external variable. Two hundred and six nursing students participated in this study. The findings suggest that the system was perceived as useful, and that the students felt confident working with computers and intended to review RSI in SL as often as needed. However, they remained neutral regarding the ease of use of the system. Strategies were suggested for boosting the students’ self-confidence in using the system. Overall use of the TAM in this context was successful, indicating the robustness of the model. The limitations of the study were discussed and further areas of research on the TAM were proposed.